Recent Advancement and Novel Application of Natural Polyphenols for the Treatment of Allergy Asthma: From Phytochemistry to Biological Implications.

Allergic diseases, primarily IgE-mediated, exert a substantial global health burden. A pivotal role in allergic reactions is played by mast cells, with histamine serving as a central mediator. Within this context, plant-based polyphenols, abundantly present in vegetables and fruits, show promising potential for allergy prevention. These natural compounds, particularly flavonoids, possess anti-inflammatory and anti-allergic properties, influencing dendritic cells, modulating macrophages, and fostering the proliferation of B cells and T cells. The potent anti-allergic effects of flavonoids are attributed to their ability to reduce the production of signaling factors, suppress cytokine production, and regulate signal transduction and gene expression in mast cells, basophils, and T cells. Notably, their benefits extend beyond allergy prevention, as they hold promise in the prevention and treatment of autoimmune illnesses such as diabetes, rheumatoid arthritis, and multiple sclerosis. In the context of allergic reactions and autoimmune diseases, polyphenols exhibit immunomodulatory effects by inhibiting autoimmune T cell proliferation and downregulating pro-inflammatory cytokines. In recent times, flavonoids, being the most prevalent polyphenols in food, have garnered significant attention from researchers due to their potential health advantages. This review compiles the latest scientific research to highlight the impact of flavonoids on allergic illnesses and their potential as a beneficial dietary component.

Structural and functional characterization of the transcriptional regulator Rv3488 of Mycobacterium tuberculosis H37Rv.

Rv3488 of Mycobacterium tuberculosis H37Rv has been assigned to the phenolic acid decarboxylase repressor (PadR) family of transcriptional regulators that play key roles in multidrug resistance and virulence of prokaryotes. The binding of cadmium, zinc, and several other metals to Rv3488 was discovered and characterized by isothermal titration calorimetery to be an exothermic process. Crystal structures of apo-Rv3488 and Rv3488 in complex with cadmium or zinc ions were determined by X-ray crystallography. The structure of Rv3488 revealed a dimeric protein with N-terminal winged-helix-turn-helix DNA-binding domains composed of helices α1, α2, α3, and strands ß1 and ß2, with the dimerization interface being formed of helices α4 and α1. The overall fold of Rv3488 was similar to PadR-s2 and metal sensor transcriptional regulators. In the crystal structure of Rv3488-Cd complex, two octahedrally coordinated Cd2+ ions were present, one for each subunit. The same sites were occupied by zinc ions in the structure of Rv3488-Zn, with two additional zinc ions complexed in one monomer. EMSA studies showed specific binding of Rv3488 with its own 30-bp promoter DNA. The functional role of Rv3488 was characterized by expressing the rv3488 gene under the control of hsp60 promoter in Mycobacterium smegmatis Expression of Rv3488 increased the intracellular survival of recombinant M. smegmatis in murine macrophage cell line J774A.1 and also augmented its tolerance to Cd2+ ions. Overall, the studies show that Rv3488 may have transcription regulation and metal-detoxifying functions and its expression in M. smegmatis increases intracellular survival, perhaps by counteracting toxic metal stress.

Trauma and Health Symptoms in a Community Sample: Examining the Influences of Gender and Daily Stress.

Although there is a rich body of literature on trauma and health, limited research has investigated the variables of gender, trauma symptoms, physical health, mental health, and daily stress together in a community sample. Considering the deleterious effects of trauma on health, our overarching inquiry was whether trauma symptoms can predict overall mental and physical health with attention to gender and daily stress as potential moderators. Participants (n = 103; 50.5% women) completed self-report measures of trauma symptoms, mental health, physical health, and daily stress, along with demographic information. Trauma symptoms predicted 25.2% of the variance in general health symptoms. Gender significantly added to the variance accounted for, but daily stress was not significant in the model. Trauma symptoms predicted 37.1% of the variance in mental health symptoms. Daily stress significantly added to the model, but gender did not. Results are interpreted through the integration of family stress theory and feminist frameworks, adding to the literature by further illuminating the relationships between gender, daily stress, health symptoms, and trauma in a community sample.

Efficacy of a Targeted Drug Delivery on-Demand Bolus Option for Chronic Pain.

BACKGROUND AND OBJECTIVES: Intrathecal targeted drug delivery systems historically required physician office visits for dose adjustment to manage fluctuating pain. A wireless device now enables patients to supplement their basal intrathecal infusion with a programmed on-demand bolus dose. We sought to quantify the change in oral breakthrough opioid need associated with the use of an intrathecal bolus in comparison to those treated with the basal infusion alone. METHODS: Demographic, dosage, bolus usage and longevity data were extracted from the historical medical record of 69 patients (18/51 bolus/nonbolus) followed continuously at our center. Medication consumption and Pain Disability Index measures were obtained at baseline and most recent follow-up. RESULTS: Among patients with the bolus option, only 2 (11%; confidence interval [CI] 0% to 26%) continued to require oral opiates to manage breakthrough pain compared to 29 (57%; CI 43% to 71%) without the bolus option. The Pain Disability Index score decreased by 19% in patients with the bolus option and by 25% in those with the basal infusion. Total daily intrathecal opioid intake was 34% lower in the group with the bolus device. CONCLUSIONS: Utilizing an intrathecal bolus to treat incident pain was a safe way to manage unpredictable breakthrough pain and may represent a cost-saving opportunity by eliminating the need for oral analgesic medications.

Natriuretic peptide testing in high-risk pregnancy: a preventive opportunity?

Natriuretic peptide testing has been widely utilized in the heart failure and cardiac patient population, but there is limited utilization during pregnancy. Patients with hypertensive diseases of pregnancy have been shown to experience elevation of circulating natriuretic peptide levels compared to normal pregnancies, especially in the setting of preeclampsia. Natriuretic peptide testing can be utilized in patients presenting with signs and symptoms suspicious of heart failure in order to rule out underlying cardiac causes. Meanwhile, monitoring natriuretic peptide levels in those with established heart diseases (both congenital and acquired) may facilitate careful management of cardiac status during the course of pregnancy. Further investigations in the judicious use of selected medications (particularly loop diuretics) in the setting of elevated natriuretic peptide levels are warranted.

Potential of Curcumin nanoemulsion as antimicrobial and wound healing agent in burn wound infection.

The review article concentrates on the potential uses of curcumin nanoemulsion in treatment and management of burn wound. Poor solubility and low bioavailability of curcumin limits the efficient and effective use of curcumin in management of bacterial infection related to burn wound. Nano particle based drug delivery system can be of great aid to solve this problem. Among this nanoemulsion is most favourable system due to its simplicity and low manufacturing cost. Nanoemulsion also enhances the skin permeation ability of curcumin and thus enhances its pharmacological efficacy specially as a potential antimicrobial agent, which can have applicability as a topical therapeutic agent in burn wound infection.

Signaling pathways and molecular process of natural polyphenols in the amelioration of inflammatory bowel disease: A privileged scaffold in new drug discovery.

BACKGROUND: GIT is seriously affected by inflammatory bowel disease (IBD), which is characterized by extreme inflammation and an imbalance in a person's healthy life span. The frequency of occurrence of such chronic diseases as IBD would continue to increase. In the past decade, increasing attention has been paid to polyphenols from natural sources have been shown to serve as successful therapeutic agents for altering the signalling pathways linked to IBD and oxidative stress. METHODS: We conducted a structured search for peer-reviewed research articles using the various keywords in bibliographic databases. By using common tools and a deductive qualitative content analysis technique, the quality of the retrieved papers and the distinctive findings of the articles included in the study were evaluated. RESULTS: Notably, experimental and clinical evidence has proved that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of IBD. Polyphenol phytochemicals have shown noticeable alleviative effects by acting on the TLR/NLR, and NF-κB signaling pathway in intestinal inflammation. CONCLUSION: This study examines the potential of polyphenols for treating IBD, with an emphasis on modulating cellular signalling mechanisms, regulating the balance of gut microbiota, and restoring the epithelial barrier. The available evidence concluded that the utilization of polyphenol-rich sources could control inflammation, mucosal healing, and positive benefits with minimal side effects. Even though additional study is required in this area, particularly that which focuses on the interactions, connections, and precise mechanisms of action linking polyphenols and IBD.

Comprehensive Analysis of Electronic Health Records to Characterize The Association Between Intimate Partner Violence and Mental Health.

Intimate partner violence (IPV) involves physical, emotional, and sexual harm to the survivor. To characterize the relationship between mental health and IPV, we utilized electronic health records (EHR) data from IBM Explorys. Focusing on 15 mental health conditions and IPV, we queried cohorts of patients with these conditions to discover additional medical terms, including symptoms, findings, and diagnoses that are prevalent in these cohorts. We then systematically assessed the (i) direct association (co-occurrence, i.e., relative prevalence of a medical term in a cohort compared to the background population) and (ii) indirect association (the similarity between co-occurrence profiles) between all pairs of these mental health conditions. Our results showed that direct and indirect measures of association provide complementary insights into the relationship between pairs of conditions. Using this framework, we discovered several patterns of association among 16 different mental health related conditions.

Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension.

BACKGROUND: Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. METHODS: We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. RESULTS: In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ±â€¯3 versus 36.6 ±â€¯3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). CONCLUSION: While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

Biophysical and immunological characterization of the ESX-4 system ESAT-6 family proteins Rv3444c and Rv3445c from Mycobacterium tuberculosis H37Rv.

The ESAT-6 family proteins of Mycobacterium tuberculosis are regarded as the key mediators in mycobacterial virulence and are largely considered as antigens that can improve TB vaccines and diagnostics. We have characterized Rv3444c and Rv3445c proteins of the ESX-4 system of ESAT-6 family of M. tuberculosis H37Rv, and have experimentally established that these two proteins interact to form a heterodimeric complex. Complex formation resulted in induction of α-helical conformation and stability against chemical denaturation. To evaluate the immunogenic potential, we have immunized mice with Rv3444c or Rv3445c along with Freund's incomplete adjuvant (FIA). Immunization with Rv3444c-FIA or Rv3445c-FIA resulted in long term humoral responses. Re-stimulation of splenocytes from immunized mice resulted in significant lymphocyte proliferation with induction of TNF-α and IL-6. Further, the humoral responses to Rv3444c and Rv3445c antigens in Indian patients with active pulmonary TB (n = 44), and healthy individuals (n = 20), were investigated. Compared to healthy individuals, high levels of IgG against Rv3444c and Rv3445c were observed in TB patient's sera, indicating that these proteins are actively produced during the active phase of TB. Cellular immune responses to these proteins in active pulmonary TB patients (n = 5) were also investigated using peripheral blood mononuclear cells (PBMCs). Both the proteins induce significant lymphocyte proliferation and up-regulate the induction of TNF-α and IL-6 in TB patients.

Two-Decade Trends in the Prevalence of Atherosclerotic Risk Factors, Coronary Plaque Morphology, and Outcomes in Adults Aged ≤45 Years Undergoing Percutaneous Coronary Intervention.

Data are limited about the prevalence trends of risk factors, lesion morphology, and clinical outcomes of coronary artery disease in patients, aged ≤45 years, undergoing percutaneous coronary intervention (PCI), between the bare-metal stent (BMS; 1994 to 2002) and drug-eluting stent (DES; 2003 to 2012) eras. From the PCI database at the Cleveland Clinic, we identified 1,640 patients aged ≤45 years and without a history of coronary artery bypass grafting who underwent PCI from 1994 to 2012. There were 883 patients in the BMS era cohort with a mean follow-up period of 13.15 years and 757 in the DES era cohort with a mean follow-up of 5.02 years. The DES era had more obese (51.8% vs 44.7%, p <0.001) and diabetes (23.0% vs 19.5%, p = 0.09) patients. DES era patients had more B2/C lesions (74.0% vs 32.5%, p <0.001), more severe preprocedural stenosis (86.1 ± 12.9 vs 72.2 ± 21.3, p <0.001), and longer lesions (15.5 ± 9.9 vs 9.6 ± 6.8, p <0.001). No difference was observed in the 30-day mortality between the DES and BMS eras. Irrespective of era, diabetics had worse long-term mortality (19.4% vs 9.3%, p <0.001) compared with nondiabetics. Obese patients had similar long-term outcomes compared with nonobese patients. In conclusion, patients aged ≤45 years, who underwent a PCI procedure in the DES era had worse risk factor profiles, including obesity, compared with patients in the BMS era. They also had more complex lesions. Procedural and long-term outcomes of these patients have not changed between the 2 eras. Young diabetic patients have worse long-term outcomes compared with nondiabetics.

Secretion of ligninperoxidase by Penicillium citrinum, Fusarium oxysporum and Aspergillus terreus.

Secretion of ligninperoxidase [E.C.1.11.1.7] by Penicillium citrinum, Fusarium oxysporum and Aspergillus terreus in liquid culture growth medium has been demonstrated. Enzymatic characteristics like Km, pH and temperature optima using veratryl alcohol as the organic substrate of ligninperoxidases from above sources have been determined. Km values using veratryl alcohol as substrate for enzymes from P. citrinum, F. oxysporum and A. terreus were 69, 64 and 60 microM respectively. Km values using H2O2 as the variable substrate were 64, 72 and 80 microM. The pH optima were 4.0, 2.3 and 2.0 respectively. The values of temperature optima were 30 degrees, 25 degrees and 22 degrees C for the enzymes from P. citrinum, F. oxysporum and A. terreus respectively.

Risk of cerebrovascular events in patients with patent foramen ovale and intracardiac devices.

OBJECTIVES: This study investigated whether patients with patent foramen ovale (PFO) have an increased risk of stroke due to permanent pacemaker (PPM)/implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND: Data are lacking on the risk of stroke in patients with PFO and implantable intracardiac devices, either a PPM or an ICD. We investigated whether patients with PFO have increased risk of stroke due to PPM/ICD implantation. METHODS: Between 2001 and 2008, 2,921 consecutive patients with PFO (67.5 ± 16.4 years of age, 52.2% male) were identified from our echocardiography database. These patients were divided into a device group (patients had PPM/ICD implantation for any reason after receiving a diagnosis of PFO) and a no device group (patients did not have PPM or ICD implantation). Patients who had PFO closure during follow-up were excluded. Both groups were matched for baseline characteristics and medications. The incidence of ischemic stroke was assessed in each group after propensity score matching (case:control ratio of 1:1 yielding 231 pairs). All patients completed at least 4 years of follow-up until May 2012. RESULTS: There were 2,690 patients in the n device group (67.3 ± 16.4 years of age, 51.6% male) and 231 patients in the device group (75.4 ± 14.6 years of age, 59.3% male). Six patients (2.6%) in the no device group and 6 (2.6%) in the device group had a stroke during the follow-up period. No difference in the rate of stroke, transient ischemic stroke, or stroke/transient ischemic stroke was observed between the 2 groups. CONCLUSIONS: The risk of stroke in patients with PFO and an implantable intracardiac device is similar to those without an intracardiac device. In patients with PFO, without a history of stroke, device implantation might not be considered a risk factor for future stroke occurrence.

Genomic and proteomic studies on the effects of the insect growth regulator diflubenzuron in the model beetle species Tribolium castaneum.

Several benzoylphenyl urea-derived insecticides such as diflubenzuron (DFB, Dimilin) are in wide use to control various insect pests. Although this class of compounds is known to disrupt molting and to affect chitin content, their precise mode of action is still not understood. To gain a broader insight into the mechanism underlying the insecticidal effects of benzoylphenyl urea compounds, we conducted a comprehensive study with the model beetle species and stored product pest Tribolium castaneum (red flour beetle) utilizing genomic and proteomic approaches. DFB was added to a wheat flour-based diet at various concentrations and fed to larvae and adults. We observed abortive molting, hatching defects and reduced chitin amounts in the larval cuticle, the peritrophic matrix and eggs. Electron microscopic examination of the larval cuticle revealed major structural changes and a loss of lamellate structure of the procuticle. We used a genomic tiling array for determining relative expression levels of about 11,000 genes predicted by the GLEAN algorithm. About 6% of all predicted genes were more than 2-fold up- or down-regulated in response to DFB treatment. Genes encoding enzymes involved in chitin metabolism were unexpectedly unaffected, but many genes encoding cuticle proteins were affected. In addition, several genes presumably involved in detoxification pathways were up-regulated. Comparative 2D gel electrophoresis of proteins extracted from the midgut revealed 388 protein spots, of which 7% were significantly affected in their levels by DFB treatment as determined by laser densitometry. Mass spectrometric identification revealed that UDP-N-acetylglucosamine pyrophosphorylase and glutathione synthetase were up-regulated. In summary, the red flour beetle turned out to be a good model organism for investigating the global effects of bioactive materials such as insect growth regulators and other insecticides. The results of this study recapitulate all of the different DFB-induced symptoms in a single model insect, which have been previously found in several different insect species, and further illustrate that DFB treatment causes a wide range of effects at the molecular level.